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Volume 17, January-2
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Cancers, Volume 17, Issue 1 (January-1 2025) – 159 articles

Cover Story (view full-size image): This review discusses the emerging paradigm that prostate cancer metastasis is driven by a dysregulation of critical molecular machinery that regulates endosome-lysosome homeostasis. Endosome and lysosome compartments have crucial roles in maintaining normal cellular function but are also involved in many hallmarks of cancer pathogenesis, including inflammation, immune response, nutrient sensing, metabolism, proliferation, signalling, and migration. Here we discuss new insight into how alterations in the complex network of trafficking machinery, responsible for the microtubule-based transport of endosomes and lysosomes, may be involved in prostate cancer progression. A better understanding of endosome-lysosome dynamics may facilitate the discovery of novel strategies to detect and manage prostate cancer metastasis and improve patient outcomes. View this paper
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26 pages, 4295 KiB  
Communication
Association of Proteasome Activity and Pool Heterogeneity with Markers Determining the Molecular Subtypes of Breast Cancer
by Irina Kondakova, Elena Sereda, Evgeniya Sidenko, Sergey Vtorushin, Valeria Vedernikova, Alexander Burov, Pavel Spirin, Vladimir Prassolov, Timofey Lebedev, Alexey Morozov and Vadim Karpov
Cancers 2025, 17(1), 159; https://doi.org/10.3390/cancers17010159 - 6 Jan 2025
Viewed by 470
Abstract
Background: Proteasomes degrade intracellular proteins. Different proteasome forms were identified. Proteasome inhibitors are used in cancer therapy, and novel drugs directed to specific proteasome forms are developed. Breast cancer (BC) therapy depends on the subtype of the tumor, determined by the expression level [...] Read more.
Background: Proteasomes degrade intracellular proteins. Different proteasome forms were identified. Proteasome inhibitors are used in cancer therapy, and novel drugs directed to specific proteasome forms are developed. Breast cancer (BC) therapy depends on the subtype of the tumor, determined by the expression level of Ki67, HER-2, estrogen and progesterone receptors. Relationships between the presence of specific proteasome forms and proteins that determine the BC subtype remain unclear. Here, using gene expression data in 19,145 tumor samples from 144 datasets and tissues from 159 patients with different subtypes of BC, we investigated the association between the activity and expression of proteasomes and levels of BC subtype markers. Methods: Bioinformatic analysis of proteasome subunit (PSMB1-10) gene expression in BC was performed. Proteasome heterogeneity in BC cell lines was investigated by qPCR. By Western blotting, proteasome composition was assessed in cells and patient tissue lysates. Proteasome activities were studied using fluorogenic substrates. BC molecular subtypes were determined by immunohistochemistry. Results: BC subtypes demonstrate differing proteasome subunit expression pattern and strong PSMB8-10 co-correlation in tumors. A significant increase in chymotrypsin- and caspase-like proteasome activities in BC compared to adjacent tissues was revealed. The subunit composition of proteasomes in tumor tissues of BC subtypes varied. Regression analysis demonstrated a positive correlation between proteasome activities and the expression of Ki67, estrogen receptors and progesterone receptors. Conclusion: BC subtypes demonstrate differences within the proteasome pool. Correlations between the proteasome activity, hormone receptors and Ki67 indicate possible mutual influence. Obtained results facilitate development of novel drug combinations for BC therapy. Full article
(This article belongs to the Section Molecular Cancer Biology)
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14 pages, 737 KiB  
Review
Congenital Dermatofibrosarcoma Protuberans—An Update on the Ongoing Diagnostic Challenges
by Fortunato Cassalia, Andrea Danese, Enrico Cocchi, Silvia Vaienti, Anna Bolzon, Ludovica Franceschin, Roberto Mazzetto, Francesca Caroppo, Davide Melandri and Anna Belloni Fortina
Cancers 2025, 17(1), 158; https://doi.org/10.3390/cancers17010158 - 6 Jan 2025
Viewed by 413
Abstract
Dermatofibrosarcoma protuberans (DFSP) is a rare, low-grade sarcoma that presents diagnostic challenges due to its resemblance to benign lesions [...] Full article
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24 pages, 1064 KiB  
Article
Impact of Early Nutritional Intervention During Cancer Treatment on Dietary Intakes and Cardiometabolic Health in Children and Adolescents
by Josianne Delorme, Andra Dima, Véronique Bélanger, Mélanie Napartuk, Isabelle Bouchard, Caroline Meloche, Daniel Curnier, Serge Sultan, Caroline Laverdière, Daniel Sinnett and Valérie Marcil
Cancers 2025, 17(1), 157; https://doi.org/10.3390/cancers17010157 - 6 Jan 2025
Viewed by 480
Abstract
Background/Objectives: Pediatric cancer survivors are at greater risk of cardiometabolic complications than their peers. This study evaluates the preliminary impact of the VIE (Valorization, Implication, Education) intervention, which integrates nutrition, physical activity, and psychological support, on dietary intake and cardiometabolic health among children [...] Read more.
Background/Objectives: Pediatric cancer survivors are at greater risk of cardiometabolic complications than their peers. This study evaluates the preliminary impact of the VIE (Valorization, Implication, Education) intervention, which integrates nutrition, physical activity, and psychological support, on dietary intake and cardiometabolic health among children and adolescents during cancer treatment. Methods: This comparative study includes pediatric cancer patients recruited to either the VIE intervention group or a control group receiving standard care. Post-treatment data on dietary intake, anthropometric measures, blood pressure, and biochemical parameters were compared between groups and stratified by level of involvement in the nutritional intervention and age at diagnosis (children and adolescents). Results: In the intervention group, 45 participants were included (51.1% male, mean age at evaluation 10.2 ± 4.5 years, mean time since end of treatment of 1.3 ± 0.8 years), and the control group comprised 77 participants (44.2% male, mean age at evaluation 12.0 ± 5.6 years, mean time since end of treatment of 1.4 ± 0.8 years). The intervention group had lower total caloric intake (mean: 1759 ± 513 vs. 1997 ± 669 kcal, p = 0.042) and higher calcium intake (mean: 567 ± 240 vs. 432 ± 197 mg/1000 kcal, p = 0.001). The participants who were highly involved in the nutritional intervention had greater protein-derived energy intake than the controls (mean: 17 ± 5 vs. 15 ± 4%, p = 0.029). While there was a tendency for a lesser proportion of cardiometabolic risk factors in the adolescents from the intervention group, the differences did not reach statistical significance. Conclusions: The VIE intervention improved some specific dietary intakes in the medium term after treatment completion but did not significantly impact cardiometabolic health outcomes. Additional strategies are needed to improve the diet of pediatric cancer patients, and further research is warranted to assess the long-term impact of such interventions. Full article
(This article belongs to the Topic Nutrition and Health During and After Childhood Cancer)
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7 pages, 214 KiB  
Editorial
Learning from Other Tumors: Pathways for Progress and Overcoming Challenges in Cholangiocarcinoma
by Giulia Tesini, Chiara Braconi, Lorenza Rimassa and Rocio I. R. Macias
Cancers 2025, 17(1), 156; https://doi.org/10.3390/cancers17010156 - 6 Jan 2025
Viewed by 517
Abstract
Cholangiocarcinoma (CCA) is a group of complex and heterogeneous tumors originating from the epithelial cells of bile ducts that can occur in intrahepatic, perihilar, or distal localizations [...] Full article
(This article belongs to the Special Issue Insights from the Editorial Board Member)
45 pages, 956 KiB  
Review
Metabolic Signaling in the Tumor Microenvironment
by Ryan Clay, Kunyang Li and Lingtao Jin
Cancers 2025, 17(1), 155; https://doi.org/10.3390/cancers17010155 - 6 Jan 2025
Viewed by 535
Abstract
Cancer cells must reprogram their metabolism to sustain rapid growth. This is accomplished in part by switching to aerobic glycolysis, uncoupling glucose from mitochondrial metabolism, and performing anaplerosis via alternative carbon sources to replenish intermediates of the tricarboxylic acid (TCA) cycle and sustain [...] Read more.
Cancer cells must reprogram their metabolism to sustain rapid growth. This is accomplished in part by switching to aerobic glycolysis, uncoupling glucose from mitochondrial metabolism, and performing anaplerosis via alternative carbon sources to replenish intermediates of the tricarboxylic acid (TCA) cycle and sustain oxidative phosphorylation (OXPHOS). While this metabolic program produces adequate biosynthetic intermediates, reducing agents, ATP, and epigenetic remodeling cofactors necessary to sustain growth, it also produces large amounts of byproducts that can generate a hostile tumor microenvironment (TME) characterized by low pH, redox stress, and poor oxygenation. In recent years, the focus of cancer metabolic research has shifted from the regulation and utilization of cancer cell-intrinsic pathways to studying how the metabolic landscape of the tumor affects the anti-tumor immune response. Recent discoveries point to the role that secreted metabolites within the TME play in crosstalk between tumor cell types to promote tumorigenesis and hinder the anti-tumor immune response. In this review, we will explore how crosstalk between metabolites of cancer cells, immune cells, and stromal cells drives tumorigenesis and what effects the competition for resources and metabolic crosstalk has on immune cell function. Full article
(This article belongs to the Special Issue Recent Updates on Cancer Stem Cells and Tumor Microenvironment)
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30 pages, 2082 KiB  
Review
The Role of Chronic Inflammation in Pediatric Cancer
by Christine Mella, Panogiotis Tsarouhas, Maximillian Brockwell and Hope C. Ball
Cancers 2025, 17(1), 154; https://doi.org/10.3390/cancers17010154 - 6 Jan 2025
Viewed by 550
Abstract
Inflammation plays a crucial role in wound healing and the host immune response following pathogenic invasion. However, unresolved chronic inflammation can result in tissue fibrosis and genetic alterations that contribute to the pathogenesis of human diseases such as cancer. Recent scientific advancements exploring [...] Read more.
Inflammation plays a crucial role in wound healing and the host immune response following pathogenic invasion. However, unresolved chronic inflammation can result in tissue fibrosis and genetic alterations that contribute to the pathogenesis of human diseases such as cancer. Recent scientific advancements exploring the underlying mechanisms of malignant cellular transformations and cancer progression have exposed significant disparities between pediatric and adult-onset cancers. For instance, pediatric cancers tend to have lower mutational burdens and arise in actively developing tissues, where cell-cycle dysregulation leads to gene, chromosomal, and fusion gene development not seen in adult-onset counterparts. As such, scientific findings in adult cancers cannot be directly applied to pediatric cancers, where unique mutations and inherent etiologies remain poorly understood. Here, we review the role of chronic inflammation in processes of genetic and chromosomal instability, the tumor microenvironment, and immune response that result in pediatric tumorigenesis transformation and explore current and developing therapeutic interventions to maintain and/or restore inflammatory homeostasis. Full article
(This article belongs to the Section Pediatric Oncology)
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10 pages, 233 KiB  
Article
Quality of Nursing Care as Perceived by Patients Treated for Multiple Myeloma in Polish Oncology Units: A Cross-Sectional Study
by Magdalena Kurek, Tomasz Tatara, Jakub Świtalski, Adam Fronczak, Magdalena Tatara and Anna Augustynowicz
Cancers 2025, 17(1), 153; https://doi.org/10.3390/cancers17010153 - 6 Jan 2025
Viewed by 394
Abstract
Background/Objectives: Patient satisfaction is one of the indicators of the quality of nursing care. The purpose of this study is to find out the level of satisfaction of patients with multiple myeloma with the quality of nursing care in oncology units. Methods: Data [...] Read more.
Background/Objectives: Patient satisfaction is one of the indicators of the quality of nursing care. The purpose of this study is to find out the level of satisfaction of patients with multiple myeloma with the quality of nursing care in oncology units. Methods: Data were obtained by a diagnostic survey method, using the Newcastle Nursing Satisfaction Scale. The survey was conducted among patients from four oncology departments in Poland on the day the patient was discharged or transferred to another unit. Participation in the study was voluntary and required patient consent. Patients were assured of the anonymity of their responses. Results: The study included 65 men and 75 women treated with chemotherapy and autologous hematopoietic stem cell transplant. Experiences and satisfaction with nursing care presented a level of 71.80 points and 74.46 points, respectively. The analysis showed no statistically significant differences between the groups in terms of treatment and gender. A statistically significant negative association was shown between age and nursing care experience score (r = −0.19; p = 0.024). Positive associations were shown between length of stay on the unit and rating of experience of nursing care (r = 0.23; p = 0.006) and satisfaction with nursing care (r = 0.26; p = 0.002). Conclusions: The experience and satisfaction with nursing care among patients treated for multiple myeloma in Polish oncology units is moderate. Efforts should be made to improve the quality of nursing care, especially taking into account the needs of the elderly. Full article
(This article belongs to the Section Cancer Survivorship and Quality of Life)
2 pages, 450 KiB  
Correction
Correction: Häyrinen et al. The Transcription Factor Twist1 Has a Significant Role in Mycosis Fungoides (MF) Cell Biology: An RNA Sequencing Study of 40 MF Cases. Cancers 2023, 15, 1527
by Marjaana J. Häyrinen, Jenni Kiiskilä, Annamari Ranki, Liisa Väkevä, Henry J. Barton, Milla E. L. Kuusisto, Katja Porvari, Hanne Kuitunen, Kirsi-Maria Haapasaari, Hanna-Riikka Teppo and Outi Kuittinen
Cancers 2025, 17(1), 152; https://doi.org/10.3390/cancers17010152 - 6 Jan 2025
Viewed by 246
Abstract
In the original publication [...] Full article
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10 pages, 2408 KiB  
Article
Benign or Malignant? Ex Vivo Confocal Laser Scanning Microscopy for Bedside Histological Assessment of Melanocytic Lesions
by Maximilian Deußing, Lisa Buttgereit, Michaela Maurer, Alisa Swarlik, Lara Stärr, Andreas Ohlmann, Katrin Kerl-French, Michael Flaig, Elke C. Sattler, Lars E. French and Daniela Hartmann
Cancers 2025, 17(1), 151; https://doi.org/10.3390/cancers17010151 - 6 Jan 2025
Viewed by 493
Abstract
Objective: Ex vivo confocal laser scanning microscopy (EVCM) is an emerging imaging technique, which offers rapid tissue examination. While the current literature shows promising results in the evaluation of non-melanoma skin cancer, only limited research exists on the application of EVCM in melanocytic [...] Read more.
Objective: Ex vivo confocal laser scanning microscopy (EVCM) is an emerging imaging technique, which offers rapid tissue examination. While the current literature shows promising results in the evaluation of non-melanoma skin cancer, only limited research exists on the application of EVCM in melanocytic lesions. This study aimed to assess the utility of EVCM in the characterization of melanocytic lesions and compare its findings with gold-standard histopathology. Methods: A total of 130 skin lesions, including 76 benign and 54 malignant melanocytic lesions, were prospectively collected and imaged using EVCM. Three blinded investigators were asked to identify characteristic morphologic features observed in the lesions and classify them into benign vs. malignant. The results were then compared with the corresponding histopathology. Sensitivity and specificity were calculated using contingency tables to assess the diagnostic performance. Results: The application of EVCM allowed for the visualization of cellular and tissue-level details, including cellular pleomorphism and atypical melanocytes. A comprehensive list of benign and malignant features identified by EVCM was compiled. Using these diagnostic criteria, the imaging of the inexperienced and dermatohistopathology-experienced investigator reached 67.7% concordance, and the imaging trained dermatologist obtained 69.2% agreement with dermatohistopathology in differentiating benign vs. malignant lesions. The imaging-trained dermatohistopathologist performed best with concordance up to 79.2%. Conclusions: In conclusion, EVCM is a promising technique for the rapid assessment of melanocytic lesions. Our study provides a comprehensive overview of morphologic EVCM features, which will contribute to the development of diagnostic algorithms for accurate diagnosis and appropriate treatment planning. Further studies are needed to evaluate its clinical utility and validate our diagnostic criteria. Full article
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17 pages, 3052 KiB  
Systematic Review
Robotic Versus Laparoscopic Adrenalectomy for Adrenal Tumors: An Up-to-Date Meta-Analysis on Perioperative Outcomes
by Giuseppe Esposito, Barbara Mullineris, Giovanni Colli, Serena Curia and Micaela Piccoli
Cancers 2025, 17(1), 150; https://doi.org/10.3390/cancers17010150 - 5 Jan 2025
Viewed by 609
Abstract
Background: Minimally invasive surgery (MIS) for adrenal glands is becoming increasingly developed worldwide and robotic surgery has advanced significantly. Although there are still concerns about the generalization of outcomes and the cost burden, the robotic platform shows several advantages in overcoming some laparoscopic [...] Read more.
Background: Minimally invasive surgery (MIS) for adrenal glands is becoming increasingly developed worldwide and robotic surgery has advanced significantly. Although there are still concerns about the generalization of outcomes and the cost burden, the robotic platform shows several advantages in overcoming some laparoscopic shortcomings. Materials and Methods: A systematic review and meta-analysis were conducted using the PubMed, MEDLINE and Cochrane library databases of published articles comparing RA and LA up to January 2024. The evaluated endpoints were technical and post-operative outcomes. Dichotomous data were calculated using the odds ratio (OR), while continuous data were analyzed usingmean difference (MD) with a 95% confidence interval (95% CI). A random-effects model (REM) was applied. Results: By the inclusion of 28 studies, the meta-analysis revealed no statistically significant difference in the rates of intraoperative RBC transfusion, 30-day mortality, intraoperative and overall postoperative complications, re-admission, R1 resection margin and operating time in the RA group compared with the LA. However, the overall cost of hospitalization was significantly higher in the RA group than in the LA group, [MD USD 4101.32, (95% CI 3894.85, 4307.79) p < 0.00001]. With respect to the mean intraoperative blood loss, conversion to open surgery rate, time to first flatus and length of hospital stay, the RA group showed slightly statistically significant lower rates than the laparoscopic approach. Conclusions: To our knowledge, this is the largest and most recent meta-analysis that makes these comparisons. RA can be considered safe, feasible and comparable to LA in terms of the intraoperative and post-operative outcomes. In the near future, RA could represent a promising complementary approachto LA for benign and small malignant adrenal masses, particularly in high-volume referral centers specializing in robotic surgery. However, further studies are needed to confirm these findings. Full article
(This article belongs to the Section Systematic Review or Meta-Analysis in Cancer Research)
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14 pages, 570 KiB  
Article
Long-Term Outcomes and Quality of Life of High-Risk Neuroblastoma Patients Treated with a Multimodal Treatment Including Anti-GD2 Immunotherapy: A Retrospective Cohort Study
by Tim Flaadt, Jonas Rehm, Thorsten Simon, Barbara Hero, Ruth L. Ladenstein, Holger N. Lode, Desiree Grabow, Sandra Nolte, Roman Crazzolara, Johann Greil, Martin Ebinger, Michael Abele, Ursula Holzer, Michaela Döring, Johannes H. Schulte, Peter Bader, Paul-Gerhardt Schlegel, Matthias Eyrich, Peter Lang, Thomas Klingebiel and Rupert Handgretingeradd Show full author list remove Hide full author list
Cancers 2025, 17(1), 149; https://doi.org/10.3390/cancers17010149 - 5 Jan 2025
Viewed by 582
Abstract
Background: The incorporation of anti-GD2 antibodies such as ch14.18/SP2/0 into the multimodal treatment of high-risk neuroblastoma (HR-NB) patients has improved their outcomes. As studies assessing the long-term outcomes, long-term sequelae, and health-related quality of life (HRQoL) of this treatment are limited, this retrospective [...] Read more.
Background: The incorporation of anti-GD2 antibodies such as ch14.18/SP2/0 into the multimodal treatment of high-risk neuroblastoma (HR-NB) patients has improved their outcomes. As studies assessing the long-term outcomes, long-term sequelae, and health-related quality of life (HRQoL) of this treatment are limited, this retrospective analysis aimed to explore these. Patients and Methods: Between 1991 and 2002, 65 children received a multimodal treatment, including ch14.18/SP2/0, for primary HR-NB. All received chemotherapy according to the NB90/NB97 trial, 51 received high-dose chemotherapy, and all received ch14.18/SP2/0 treatment. We analyzed the long-term sequelae and HRQoL (EORTC QLQ-C30), and evaluated overall and event-free survival (OS/EFS). Results: Twenty-five survivors were evaluated for HRQoL and long-term effects. All reported long-term sequelae, including ototoxicity in 16/25 (64%), cardiac toxicity in 6/25 (24%), and endocrine toxicity in 19/25 (76%) patients. Chronic diarrhea was reported in 20% of female patients. Seven patients developed autoimmune diseases. HRQoL scores were better across multiple scales than those of the matched German general population. Twenty-five-year OS and EFS were 50.8% (95% confidence interval: 31–55) and 43% (30.1–55.3), with 33 (50.8%) long-term survivors. Thirty-two patients died: 28 (43.1%) because of progression/relapse and 4 (6.2%) because of secondary neoplasms. Conclusions: Multimodal treatment, including ch14.18/SP2/0, can achieve long-term survival in HR-NB patients, with a substantial proportion of survivors reporting better HRQoL compared to the general population. All patients reported long-term side effects mostly attributable to chemotherapy and radiotherapy. The relatively high prevalence of autoimmune diseases and persistent diarrhea warrants additional longitudinal research on individuals treated with anti-GD2 antibodies. Full article
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19 pages, 10343 KiB  
Article
Integrated Analysis of Single-Cell and Bulk RNA Data Reveals Complexity and Significance of the Melanoma Interactome
by Michael J. Diaz, Jasmine T. Tran, Arthur M. Samia, Mahtab Forouzandeh, Jane M. Grant-Kels and Marjorie E. Montanez-Wiscovich
Cancers 2025, 17(1), 148; https://doi.org/10.3390/cancers17010148 - 5 Jan 2025
Viewed by 513
Abstract
Background: Despite significant strides in anti-melanoma therapies, resistance and recurrence remain major challenges. A deeper understanding of the underlying biology of these challenges is necessary for developing more effective treatment paradigms. Methods: Melanoma single-cell data were retrieved from the Broad Single Cell Portal [...] Read more.
Background: Despite significant strides in anti-melanoma therapies, resistance and recurrence remain major challenges. A deeper understanding of the underlying biology of these challenges is necessary for developing more effective treatment paradigms. Methods: Melanoma single-cell data were retrieved from the Broad Single Cell Portal (SCP11). High-dimensional weighted gene co-expression network analysis (hdWGCNA), CellChat, and ligand-receptor relative crosstalk (RC) scoring were employed to evaluate intercellular and intracellular signaling. The prognostic value of key regulatory genes was assessed via Kaplan-Meier (KM) survival analysis using the ‘SKCM-TCGA’ dataset. Results: Twenty-seven (27) gene co-expression modules were identified via hdWGCNA. Notable findings include NRAS Q61L melanomas being enriched for modules involving C19orf10 and ARF4, while BRAF V600E melanomas were enriched for modules involving ALAS1 and MYO1B. Additionally, CellChat analysis highlighted several dominant signaling pathways, namely MHC-II, CD99, and Collagen-receptor signaling, with numerous significant ligand-receptor interactions from melanocytes, including CD99-CD99 communications with cancer-associated fibroblasts, endothelial cells, NK cells, and T-cells. KM analysis revealed that higher expression of SELL, BTLA, IL2RG, PDGFA, CLDN11, ITGB3, and SPN improved overall survival, while higher FGF5 expression correlated with worse survival. Protein-protein interaction network analysis further indicated significant interconnectivity among the identified prognostic genes. Conclusions: Overall, these insights underscore critical immune interactions and potential therapeutic targets to combat melanoma resistance, paving the way for more personalized and effective treatment strategies. Full article
(This article belongs to the Collection Emerging Therapeutics in Advanced Melanoma)
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21 pages, 966 KiB  
Review
A Personalized Approach for Oligometastatic Prostate Cancer: Current Understanding and Future Directions
by Parissa Alerasool, Susu Zhou, Eric Miller, Jonathan Anker, Brandon Tsao, Natasha Kyprianou and Che-Kai Tsao
Cancers 2025, 17(1), 147; https://doi.org/10.3390/cancers17010147 - 5 Jan 2025
Viewed by 579
Abstract
Oligometastatic prostate cancer (OMPC) represents an intermediate state in the progression from localized disease to widespread metastasis when the radiographically significant sites are limited in number and location. With no clear consensus on a definition, its diagnostic significance and associated optimal therapeutic approach [...] Read more.
Oligometastatic prostate cancer (OMPC) represents an intermediate state in the progression from localized disease to widespread metastasis when the radiographically significant sites are limited in number and location. With no clear consensus on a definition, its diagnostic significance and associated optimal therapeutic approach remain controversial, posing a significant challenge for clinicians. The current standard of care for metastatic disease is to start systemic therapy; however, active surveillance and targeted radiotherapy have become attractive options to mitigate the long-term effects of androgen deprivation therapy (ADT). Furthermore, evolving biomarker methodologies may further define optimal treatment selection. In this review, we summarize the current understanding that guides the treatment of OMPC, with a focus on how host response can be an important contributing factor. Evolving scientific understanding and clinical development will continue to shape the landscape of treatment strategies for this distinct disease state. Full article
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17 pages, 303 KiB  
Review
Glioblastoma: Clinical Presentation, Multidisciplinary Management, and Long-Term Outcomes
by David Sipos, Bence L. Raposa, Omar Freihat, Mihály Simon, Nejc Mekis, Patrizia Cornacchione and Árpád Kovács
Cancers 2025, 17(1), 146; https://doi.org/10.3390/cancers17010146 - 5 Jan 2025
Viewed by 677
Abstract
Glioblastoma, the most common and aggressive primary brain tumor in adults, presents a formidable challenge due to its rapid progression, treatment resistance, and poor survival outcomes. Standard care typically involves maximal safe surgical resection, followed by fractionated external beam radiation therapy and concurrent [...] Read more.
Glioblastoma, the most common and aggressive primary brain tumor in adults, presents a formidable challenge due to its rapid progression, treatment resistance, and poor survival outcomes. Standard care typically involves maximal safe surgical resection, followed by fractionated external beam radiation therapy and concurrent temozolomide chemotherapy. Despite these interventions, median survival remains approximately 12–15 months, with a five-year survival rate below 10%. Prognosis is influenced by factors such as patient age, molecular characteristics, and the extent of resection. Patients with IDH-mutant tumors or methylated MGMT promoters generally have improved survival, while recurrent glioblastoma is associated with a median survival of only six months, as therapies in these cases are often palliative. Innovative treatments, including TTFields, add incremental survival benefits, extending median survival to around 20.9 months for eligible patients. Symptom management—addressing seizures, headaches, and neurological deficits—alongside psychological support for patients and caregivers is essential to enhance quality of life. Emerging targeted therapies and immunotherapies, though still limited in efficacy, show promise as part of an evolving treatment landscape. Continued research and clinical trials remain crucial to developing more effective treatments. This multidisciplinary approach, incorporating diagnostics, personalized therapy, and supportive care, aims to improve outcomes and provides a hopeful foundation for advancing glioblastoma management. Full article
(This article belongs to the Special Issue Outcomes in Glioblastoma Patients: From Diagnosis to Palliation)
13 pages, 1558 KiB  
Article
Oral Maintenance Therapy in Early Breast Cancer—How Many Patients Are Potential Candidates?
by Nikolas Tauber, Lisbeth Hilmer, Dominik Dannehl, Franziska Fick, Franziska Hemptenmacher, Natalia Krawczyk, Thomas Meyer-Lehnert, Kay Milewski, Henriette Princk, Andreas Hartkopf, Achim Rody and Maggie Banys-Paluchowski
Cancers 2025, 17(1), 145; https://doi.org/10.3390/cancers17010145 - 5 Jan 2025
Viewed by 676
Abstract
Background/Objectives: This single-center analysis evaluated the number of potential candidates for endocrine-based oral maintenance therapy in a real-world setting, focusing on three therapeutic agents, namely, olaparib, abemaciclib, and ribociclib, for patients with hormone receptor-positive HER2-negative early breast cancer. Methods: All breast cancer cases [...] Read more.
Background/Objectives: This single-center analysis evaluated the number of potential candidates for endocrine-based oral maintenance therapy in a real-world setting, focusing on three therapeutic agents, namely, olaparib, abemaciclib, and ribociclib, for patients with hormone receptor-positive HER2-negative early breast cancer. Methods: All breast cancer cases from the past 10 years (n = 3230) that underwent treatment at the certified Breast Cancer Center of the Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Lübeck Campus, were analyzed. Results: Of a total of 2038 patients with HR+ HER2− eBC, 685 patients (33.6%) qualified for one or more of the three agents—olaparib, abemaciclib, and ribociclib. Of these 685 patients, 523 patients (76.4%) had node-positive and 162 (23.6%) node-negative disease. Moreover, 368 patients (18.1% of a total of 2038 patients with HR+ HER2− eBC) were eligible exclusively for ribociclib, including all node-negative patients. A total of 141 patients (6.9%) met the criteria for all three agents. In contrast, 1353 patients (66.4%) had no indication for combined endocrine therapy. Conclusions: To our knowledge, this is the largest analysis addressing all three therapeutic strategies for combined endocrine therapy. The broad indication criteria of the NATALEE study may increase clinic workloads due to more frequent physician/patient interactions. It also remains unclear how therapy recommendations will influence actual treatment, as increased visits and potential side effects could affect patient compliance and adherence. Full article
(This article belongs to the Special Issue Advances in Invasive Breast Cancer: Treatment and Prognosis)
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19 pages, 792 KiB  
Review
Recurrent and Metastatic Head and Neck Cancer: Mechanisms of Treatment Failure, Treatment Paradigms, and New Horizons
by William T. Barham, Marshall Patrick Stagg, Rula Mualla, Michael DiLeo and Sagar Kansara
Cancers 2025, 17(1), 144; https://doi.org/10.3390/cancers17010144 - 5 Jan 2025
Viewed by 533
Abstract
Background: Head and neck cancer is a deadly disease with over 500,000 cases annually worldwide. Metastatic head and neck cancer accounts for a large proportion of the mortality associated with this disease. Many advances have been made in our understanding of the mechanisms [...] Read more.
Background: Head and neck cancer is a deadly disease with over 500,000 cases annually worldwide. Metastatic head and neck cancer accounts for a large proportion of the mortality associated with this disease. Many advances have been made in our understanding of the mechanisms of metastasis. The application of immunotherapy to locally recurrent or metastatic head and neck cancer has not only improved oncologic outcomes but has also provided valuable insights into the mechanisms of immune evasion and ultimately treatment failure. Objectives: This review paper will review our current understanding of biological mechanisms of treatment failure and metastasis. Published and ongoing clinical trials in the management of metastatic head and neck cancer will also be summarized. Methods: A narrative review was conducted to address the current understanding of the mechanisms of treatment failure and current treatment paradigms in recurrent and metastatic head and neck carcinoma. Conclusions: Our understanding of treatment failure in this disease is rapidly evolving. Immunotherapy represents a valuable new tool in the fight against recurrent and metastatic head and neck squamous cell carcinoma. Integrating patient and tumor specific data via artificial intelligence and deep learning will allow for a precision oncology approach, thereby achieving better prognostication and management of patients with this deadly disease. Full article
(This article belongs to the Collection Advances in Diagnostics and Treatment of Head and Neck Cancer)
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14 pages, 1438 KiB  
Article
Adjuvant Immunotherapy After Resected Melanoma: Survival Outcomes, Prognostic Factors and Patterns of Relapse
by Sergio Martinez-Recio, Maria Alejandra Molina-Pérez, Eva Muñoz-Couselo, Alberto R. Sevillano-Tripero, Francisco Aya, Ana Arance, Mayra Orrillo, Juan Martin-Liberal, Luis Fernandez-Morales, Rocio Lesta, María Quindós-Varela, Maria Nieva, Joana Vidal, Daniel Martinez-Perez, Andrés Barba and Margarita Majem
Cancers 2025, 17(1), 143; https://doi.org/10.3390/cancers17010143 - 5 Jan 2025
Viewed by 447
Abstract
Background: Anti-PD-1-based immunotherapy has improved outcomes in stage IIB to IV resected melanoma patients in clinical trials. However, little is known about real-world outcomes, prognostic factors and patterns of relapse. Methods: This is a retrospective multicenter observational study including patients with resected melanoma [...] Read more.
Background: Anti-PD-1-based immunotherapy has improved outcomes in stage IIB to IV resected melanoma patients in clinical trials. However, little is known about real-world outcomes, prognostic factors and patterns of relapse. Methods: This is a retrospective multicenter observational study including patients with resected melanoma treated with subsequent anti-PD-1-based adjuvant immunotherapy. Data on clinical and demographic characteristics, delivered treatment, prognostic factors, time and pattern of relapse were collected. Results: We included 245 patients from eight centers; 4% of patients were at stage IIB-C, 80% at stage IIIA-D and 16% at stage IV. Recurrence-free survival (RFS) rates at 18 and 36 months were 60% and 48%, respectively, with a median RFS of 33.7 months. Prognostic factors associated with recurrence were melanoma primary site (HR 2.64, 95% CI 1.15–6.01) and starting adjuvant therapy more than 12 weeks after the last resection (HR 1.68, 95% CI 1.13–2.5); presence of serious immune-related adverse events was associated with better RFS (HR 0.4, 95% CI 0.19–0.87). Early relapses accounted for 63% of the total recurrences, with a higher number of metastatic sites (18%); in contrast, late relapses presented more frequently with brain metastases (20%). Conclusions: In our patients with resected melanoma who underwent anti-PD-1-based adjuvant immunotherapy, survival outcomes were worse than those reported in clinical trials. Primary melanoma site and time interval between the last resection and the start of adjuvant therapy were associated with survival. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Cutaneous Melanoma)
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19 pages, 980 KiB  
Review
Menin Inhibitors: New Targeted Therapies for Specific Genetic Subtypes of Difficult-to-Treat Acute Leukemias
by Pasquale Niscola, Valentina Gianfelici, Marco Giovannini, Daniela Piccioni, Carla Mazzone and Paolo de Fabritiis
Cancers 2025, 17(1), 142; https://doi.org/10.3390/cancers17010142 - 4 Jan 2025
Viewed by 773
Abstract
Menin (MEN1) is a well-recognized powerful tumor promoter in acute leukemias (AL) with KMT2A rearrangements (KMT2Ar, also known as MLL) and mutant nucleophosmin 1 (NPM1m) acute myeloid leukemia (AML). MEN1 is essential for sustaining leukemic transformation due to its interaction with wild-type KMT2A [...] Read more.
Menin (MEN1) is a well-recognized powerful tumor promoter in acute leukemias (AL) with KMT2A rearrangements (KMT2Ar, also known as MLL) and mutant nucleophosmin 1 (NPM1m) acute myeloid leukemia (AML). MEN1 is essential for sustaining leukemic transformation due to its interaction with wild-type KMT2A and KMT2A fusion proteins, leading to the dysregulation of KMT2A target genes. MEN1 inhibitors (MIs), such as revumenib, ziftomenib, and other active small molecules, represent a promising new class of therapies currently under clinical development. By disrupting the MEN1-KMT2Ar complex, a group of proteins involved in chromatin remodeling, MIs induce apoptosis and differentiation AL expressing KMT2Ar or NPM1m AML. Phase I and II clinical trials have evaluated MIs as standalone treatments and combined them with other synergistic drugs, yielding promising results. These trials have demonstrated notable response rates with manageable toxicities. Among MIs, ziftomenib received orphan drug and breakthrough therapy designations from the European Medicines Agency in January 2024 and the Food and Drug Administration (FDA) in April 2024, respectively, for treating R/R patients with NPM1m AML. Additionally, in November 2024, the FDA approved revumenib for treating R/R patients with KMT2Ar-AL. This review focuses on the pathophysiology of MI-sensitive AL, primarily AML. It illustrates data from clinical trials and discusses the emergence of resistance mechanisms. In addition, we outline future directions for the use of MIs and emphasize the need for further research to fully realize the potential of these novel compounds, especially in the context of specific genetic subtypes of challenging AL. Full article
(This article belongs to the Section Cancer Therapy)
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19 pages, 6330 KiB  
Article
Characterisation of Castration-Resistant Cell-Derived Exosomes and Their Effect on the Metastatic Phenotype
by Jorge Recio-Aldavero, Lorena Parra-Gutiérrez, Laura Muñoz-Moreno, Irene D. Román, María Isabel Arenas and Ana M. Bajo
Cancers 2025, 17(1), 141; https://doi.org/10.3390/cancers17010141 - 4 Jan 2025
Viewed by 466
Abstract
Background/Objectives: Prostate cancer (PCa) is characterised by its progression to a metastatic and castration-resistant phase. Prostate tumour cells release small extracellular vesicles or exosomes which are taken up by target cells and can potentially facilitate tumour growth and metastasis. The present work studies [...] Read more.
Background/Objectives: Prostate cancer (PCa) is characterised by its progression to a metastatic and castration-resistant phase. Prostate tumour cells release small extracellular vesicles or exosomes which are taken up by target cells and can potentially facilitate tumour growth and metastasis. The present work studies the effect of exosomes from cell lines that are representative of the different stages of the disease on the tumoral phenotype of PC3 cells. Methods: Exosomes were isolated by ultracentrifugation from human prostate epithelial cells (RWPE-1) and androgen-dependent PCa cells (LNCaP) and castration-resistant PCa cells (CRPC) with moderate (DU145) or high (PC3) metastatic capacity. The biophysical and biochemical properties of the exosomes were characterised as well as their effects on PC3 cell viability and migration. Results: The study of the exosomes of prostate cell lines shows heterogeneity in their size, presenting in some of them two types of populations; in both populations, a larger size in those derived from PC3 cells and a smaller size in those derived from non-tumourigenic prostate cells were detected. Differences were found in the physical properties of those derived from healthy and PCa cells, as well as between cells representative of the most aggressive stages of the disease. The highest gamma-glutamyl transferase (GGT) activity was observed in androgen-dependent cells and differences in the pro-metalloproteinases (MMP) activity were detected in healthy cells and in castration-resistant cells with moderate metastatic capacity with respect to PC3 cells. The treatment of PC3 cells with their own exosomes increased PC3 cell viability and migration. Conclusion: Exosomes represent a promising field of research in the diagnosis, prognosis, and treatment of prostate cancer. Full article
(This article belongs to the Special Issue Exosomes in Cancer Metastasis)
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13 pages, 3107 KiB  
Article
Maxillectomy Guided by 3D Printing Versus Conventional Surgery for Patients with Head and Neck Cancer
by Sung Yool Park, Sung Ha Jung, Anna Seo, Hakjong Noh, Hwansun Lee, Hyo Jun Kim, Younghac Kim, Man Ki Chung, Han-Sin Jeong, Chung-Hwan Baek, Young-Ik Son and Nayeon Choi
Cancers 2025, 17(1), 140; https://doi.org/10.3390/cancers17010140 - 4 Jan 2025
Viewed by 428
Abstract
Background: This study evaluates the impact of three-dimensional (3D) printing-guided maxillectomy compared with conventional maxillectomy on surgical precision and oncological outcomes in patients with head and neck cancer. Materials and Methods: A retrospective analysis was conducted on 42 patients undergoing maxillectomy (16 in [...] Read more.
Background: This study evaluates the impact of three-dimensional (3D) printing-guided maxillectomy compared with conventional maxillectomy on surgical precision and oncological outcomes in patients with head and neck cancer. Materials and Methods: A retrospective analysis was conducted on 42 patients undergoing maxillectomy (16 in a 3D printing-guided group and 26 in a conventional group). Patient demographics, tumor characteristics, and outcomes were compared. Survival outcomes were analyzed using the Kaplan–Meier method. Results: The 3D printing group showed higher rates of negative resection margins (81.3% vs. 76.9%) compared with the conventional group and a trend toward improved 5-year local recurrence-free survival (87.5% vs. 58.7%, respectively) and overall survival (84.4% vs. 70.1%, respectively). However, the differences were not statistically significant. Conclusions: Maxillectomy guided by 3D printing may offer enhanced surgical precision and improved local control in patients undergoing head and neck cancer surgeries. Further research with larger cohorts is necessary to confirm these findings. Full article
(This article belongs to the Special Issue Advancements in Head and Neck Cancer Surgery)
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13 pages, 2767 KiB  
Article
A Digital Phenotypic Assessment in Neuro-Oncology (DANO): A Pilot Study on Sociability Changes in Patients Undergoing Treatment for Brain Malignancies
by Francesca Siddi, Patrick Emedom-Nnamdi, Michael P. Catalino, Aakanksha Rana, Alessandro Boaro, Hassan Y. Dawood, Francesco Sala, Jukka-Pekka Onnela and Timothy R. Smith
Cancers 2025, 17(1), 139; https://doi.org/10.3390/cancers17010139 - 4 Jan 2025
Viewed by 450
Abstract
Background: The digital phenotyping tool has great potential for the deep characterization of neurological and quality-of-life assessments in brain tumor patients. Phone communication activities (details on call and text use) can provide insight into the patients’ sociability. Methods: We prospectively collected digital-phenotyping data [...] Read more.
Background: The digital phenotyping tool has great potential for the deep characterization of neurological and quality-of-life assessments in brain tumor patients. Phone communication activities (details on call and text use) can provide insight into the patients’ sociability. Methods: We prospectively collected digital-phenotyping data from six brain tumor patients. The data were collected using the Beiwe application installed on their personal smartphones. We constructed several daily sociability features from phone communication logs, including the number of incoming and outgoing text messages and calls, the length of messages and duration of calls, message reciprocity, the number of communication partners, and number of missed calls. We compared variability in these sociability features against those obtained from a control group, matched for age and sex, selected among patients with a herniated disc. Results: In brain tumor patients, phone-based communication appears to deteriorate with time, as evident in the trend for total outgoing minutes, total outgoing calls, and call out-degree. Conclusions: These measures indicate a possible decrease in sociability over time in brain tumor patients that may correlate with survival. This exploratory analysis suggests that a quantifiable digital sociability phenotype exists and is comparable for patients with different survival outcomes. Overall, assessing neurocognitive function using digital phenotyping appears promising. Full article
(This article belongs to the Special Issue Novel Diagnostic and Therapeutic Approaches in Diffuse Gliomas)
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10 pages, 233 KiB  
Article
Exploring the Role of Symptom Diversity in Facial Basal Cell Carcinoma: Key Insights into Preoperative Quality of Life and Disease Progression
by Domantas Stundys, Alvija Kučinskaitė, Simona Gervickaitė, Jūratė Grigaitienė, Janina Tutkuvienė and Ligita Jančorienė
Cancers 2025, 17(1), 138; https://doi.org/10.3390/cancers17010138 - 4 Jan 2025
Viewed by 375
Abstract
Facial basal cell carcinoma (BCC) is the most common skin cancer, yet delays in diagnosis and treatment persist. These delays affect quality of life (QoL), advance disease progression, and increase healthcare burden. This study explores the relationship between symptom diversity, QoL, and care-seeking [...] Read more.
Facial basal cell carcinoma (BCC) is the most common skin cancer, yet delays in diagnosis and treatment persist. These delays affect quality of life (QoL), advance disease progression, and increase healthcare burden. This study explores the relationship between symptom diversity, QoL, and care-seeking behaviors, focusing on the impact of symptoms on clinical outcomes and consultation timing. A total of 278 adults with histologically confirmed facial BCC underwent surgical treatment at Vilnius University Hospital from November 2022 to April 2024. The data collected included demographics, tumor characteristics, and self-reported symptoms (pain, bleeding, itching, tumor presence, discomfort, and erosion). Disease-specific QoL was assessed using the Skin Cancer Index. ANCOVA compared QoL across symptom groups, multiple regression analyzed symptom effects on QoL, and logistic regression evaluated care-seeking behavior over time. Cox regression assessed symptom associations with time to medical consultation. The mean time from symptom onset to consultation was 21 months. Tumor presence (27%), erosion (18%), and discomfort (17%) were the most reported symptoms. Discomfort significantly reduced QoL in emotional, social, and appearance domains (p < 0.05). Logistic regression showed tumor presence and pain were associated with earlier care-seeking within 12 months (p < 0.05). Other symptoms, such as bleeding, itching, and erosion, did not significantly influence consultation timing. The findings highlight the need for public education and proactive patient counseling to promote timely intervention and reduce the disease progression. Full article
(This article belongs to the Special Issue Advances in Skin Cancer: Diagnosis, Treatment and Prognosis)
15 pages, 4485 KiB  
Article
AI-Driven Enhancement of Skin Cancer Diagnosis: A Two-Stage Voting Ensemble Approach Using Dermoscopic Data
by Tsu-Man Chiu, Yun-Chang Li, I-Chun Chi and Ming-Hseng Tseng
Cancers 2025, 17(1), 137; https://doi.org/10.3390/cancers17010137 - 3 Jan 2025
Viewed by 600
Abstract
Background: Skin cancer is the most common cancer worldwide, with melanoma being the deadliest type, though it accounts for less than 5% of cases. Traditional skin cancer detection methods are effective but are often costly and time-consuming. Recent advances in artificial intelligence have [...] Read more.
Background: Skin cancer is the most common cancer worldwide, with melanoma being the deadliest type, though it accounts for less than 5% of cases. Traditional skin cancer detection methods are effective but are often costly and time-consuming. Recent advances in artificial intelligence have improved skin cancer diagnosis by helping dermatologists identify suspicious lesions. Methods: The study used datasets from two ethnic groups, sourced from the ISIC platform and CSMU Hospital, to develop an AI diagnostic model. Eight pre-trained models, including convolutional neural networks and vision transformers, were fine-tuned. The three best-performing models were combined into an ensemble model, which underwent multiple random experiments to ensure stability. To improve diagnostic accuracy and reduce false negatives, a two-stage classification strategy was employed: a three-class model for initial classification, followed by a binary model for secondary prediction of benign cases. Results: In the ISIC dataset, the false negative rate for malignant lesions was significantly reduced, and the number of malignant cases misclassified as benign dropped from 124 to 45. In the CSMUH dataset, false negatives for malignant cases were completely eliminated, reducing the number of misclassified malignant cases to zero, resulting in a notable improvement in diagnostic precision and a reduction in the false negative rate. Conclusions: Through the proposed method, the study demonstrated clear success in both datasets. First, a three-class AI model can assist doctors in distinguishing between melanoma patients who require urgent treatment, non-melanoma skin cancer patients who can be treated later, and benign cases that do not require intervention. Subsequently, a two-stage classification strategy effectively reduces false negatives in malignant lesions. These findings highlight the potential of AI technology in skin cancer diagnosis, particularly in resource-limited medical settings, where it could become a valuable clinical tool to improve diagnostic accuracy, reduce skin cancer mortality, and reduce healthcare costs. Full article
(This article belongs to the Special Issue Recent Advances in Skin Cancers)
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19 pages, 2749 KiB  
Review
Prioritizing Context-Dependent Cancer Gene Signatures in Networks
by Enrico Capobianco, Thomas S. Lisse and Sandra Rieger
Cancers 2025, 17(1), 136; https://doi.org/10.3390/cancers17010136 - 3 Jan 2025
Viewed by 400
Abstract
There are numerous ways of portraying cancer complexity based on combining multiple types of data. A common approach involves developing signatures from gene expression profiles to highlight a few key reproducible features that provide insight into cancer risk, progression, or recurrence. Normally, a [...] Read more.
There are numerous ways of portraying cancer complexity based on combining multiple types of data. A common approach involves developing signatures from gene expression profiles to highlight a few key reproducible features that provide insight into cancer risk, progression, or recurrence. Normally, a selection of such features is made through relevance or significance, given a reference context. In the case of highly metastatic cancers, numerous gene signatures have been published with varying levels of validation. Then, integrating the signatures could potentially lead to a more comprehensive view of the connection between cancer and its phenotypes by covering annotations not fully explored in individual studies. This broader understanding of disease phenotypes would improve the predictive accuracy of statistical models used to identify meaningful associations. We present an example of this approach by reconciling a great number of published signatures into meta-signatures relevant to Osteosarcoma (OS) metastasis. We generate a well-annotated and interpretable interactome network from integrated OS gene expression signatures and identify key nodes that regulate essential aspects of metastasis. While the connected signatures link diverse prognostic measurements for OS, the proposed approach is applicable to any type of cancer. Full article
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18 pages, 5480 KiB  
Article
A Novel In Vitro Model of the Bone Marrow Microenvironment in Acute Myeloid Leukemia Identifies CD44 and Focal Adhesion Kinase as Therapeutic Targets to Reverse Cell Adhesion-Mediated Drug Resistance
by Eleni E. Ladikou, Kim Sharp, Fabio A. Simoes, John R. Jones, Thomas Burley, Lauren Stott, Aimilia Vareli, Emma Kennedy, Sophie Vause, Timothy Chevassut, Amarpreet Devi, Iona Ashworth, David M. Ross, Tanja Nicole Hartmann, Simon A. Mitchell, Chris J. Pepper, Giles Best and Andrea G. S. Pepper
Cancers 2025, 17(1), 135; https://doi.org/10.3390/cancers17010135 - 3 Jan 2025
Viewed by 577
Abstract
Background/Objectives: Acute myeloid leukemia (AML) is an aggressive neoplasm. Although most patients respond to induction therapy, they commonly relapse due to recurrent disease in the bone marrow microenvironment (BMME). So, the disruption of the BMME, releasing tumor cells into the peripheral circulation, has [...] Read more.
Background/Objectives: Acute myeloid leukemia (AML) is an aggressive neoplasm. Although most patients respond to induction therapy, they commonly relapse due to recurrent disease in the bone marrow microenvironment (BMME). So, the disruption of the BMME, releasing tumor cells into the peripheral circulation, has therapeutic potential. Methods: Using both primary donor AML cells and cell lines, we developed an in vitro co-culture model of the AML BMME. We used this model to identify the most effective agent(s) to block AML cell adherence and reverse adhesion-mediated treatment resistance. Results: We identified that anti-CD44 treatment significantly increased the efficacy of cytarabine. However, some AML cells remained adhered, and transcriptional analysis identified focal adhesion kinase (FAK) signaling as a contributing factor; the adhered cells showed elevated FAK phosphorylation that was reduced by the FAK inhibitor, defactinib. Importantly, we demonstrated that anti-CD44 and defactinib were highly synergistic at diminishing the adhesion of the most primitive CD34high AML cells in primary autologous co-cultures. Conclusions: Taken together, we identified anti-CD44 and defactinib as a promising therapeutic combination to release AML cells from the chemoprotective AML BMME. As anti-CD44 is already available as a recombinant humanized monoclonal antibody, the combination of this agent with defactinib could be rapidly tested in AML clinical trials. Full article
(This article belongs to the Special Issue Targeting the Tumor Microenvironment (Volume II))
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14 pages, 1383 KiB  
Article
Impact of the COVID-19 Pandemic on Histopathological Cancer Diagnostics in Lower Silesia: A Comparative Analysis of Prostate, Breast, and Colorectal Cancer from 2018 to 2022
by Danuta Szkudlarek, Katarzyna Kalinowska and Benita Wiatrak
Cancers 2025, 17(1), 134; https://doi.org/10.3390/cancers17010134 - 3 Jan 2025
Viewed by 455
Abstract
Background/Objective: The COVID-19 pandemic significantly disrupted healthcare systems worldwide including cancer diagnostics. This study aimed to assess the impact of the pandemic on histopathological cancer diagnostics in Lower Silesia, Poland, specifically focusing on prostate, breast, and colorectal cancer cases from 2018 to 2022. [...] Read more.
Background/Objective: The COVID-19 pandemic significantly disrupted healthcare systems worldwide including cancer diagnostics. This study aimed to assess the impact of the pandemic on histopathological cancer diagnostics in Lower Silesia, Poland, specifically focusing on prostate, breast, and colorectal cancer cases from 2018 to 2022. The objective was to evaluate diagnostic volumes and trends before, during, and after the pandemic and to understand the effect of healthcare disruptions on cancer detection. Methods: Histopathological and cytological data were collected from multiple laboratories across Lower Silesia. Samples were categorized into three periods: pre-pandemic (January 2018–February 2020), pandemic (March 2020–May 2022), and post-pandemic (June–December 2022). Statistical analyses included comparisons of diagnostic volumes and positive diagnoses across these periods. Results: A significant reduction in the number of histopathological examinations occurred during the pandemic, particularly during its early phase. This decline was accompanied by a higher frequency of positive cancer diagnoses, suggesting the prioritization of high-risk cases. Post-pandemic, diagnostic activity showed partial recovery, though it remained below the pre-pandemic levels, with notable differences across cancer types. Conclusions: The COVID-19 pandemic significantly disrupted cancer diagnostics in Lower Silesia, delaying detection and highlighting healthcare system vulnerabilities. These findings underscore the importance of resilient healthcare systems that can ensure the continuity of essential diagnostic services and address inequalities in access to care during crises. Full article
(This article belongs to the Special Issue How COVID-19 Affects Cancer Patients)
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32 pages, 3337 KiB  
Review
Exploring the Metabolic Impact of FLASH Radiotherapy
by Febe Geirnaert, Lisa Kerkhove, Pierre Montay-Gruel, Thierry Gevaert, Inès Dufait and Mark De Ridder
Cancers 2025, 17(1), 133; https://doi.org/10.3390/cancers17010133 - 3 Jan 2025
Viewed by 585
Abstract
FLASH radiotherapy (FLASH RT) is an innovative modality in cancer treatment that delivers ultrahigh dose rates (UHDRs), distinguishing it from conventional radiotherapy (CRT). FLASH RT has demonstrated the potential to enhance the therapeutic window by reducing radiation-induced damage to normal tissues while maintaining [...] Read more.
FLASH radiotherapy (FLASH RT) is an innovative modality in cancer treatment that delivers ultrahigh dose rates (UHDRs), distinguishing it from conventional radiotherapy (CRT). FLASH RT has demonstrated the potential to enhance the therapeutic window by reducing radiation-induced damage to normal tissues while maintaining tumor control, a phenomenon termed the FLASH effect. Despite promising outcomes, the precise mechanisms underlying the FLASH effect remain elusive and are a focal point of current research. This review explores the metabolic and cellular responses to FLASH RT compared to CRT, with particular focus on the differential impacts on normal and tumor tissues. Key findings suggest that FLASH RT may mitigate damage in healthy tissues via altered reactive oxygen species (ROS) dynamics, which attenuate downstream oxidative damage. Studies indicate the FLASH RT influences iron metabolism and lipid peroxidation pathways differently than CRT. Additionally, various studies indicate that FLASH RT promotes the preservation of mitochondrial integrity and function, which helps maintain apoptotic pathways in normal tissues, attenuating damage. Current knowledge of the metabolic influences following FLASH RT highlights its potential to minimize toxicity in normal tissues, while also emphasizing the need for further studies in biologically relevant, complex systems to better understand its clinical potential. By targeting distinct metabolic pathways, FLASH RT could represent a transformative advance in RT, ultimately improving the therapeutic window for cancer treatment. Full article
(This article belongs to the Special Issue Feature Paper in Section “Cancer Therapy” in 2024)
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11 pages, 2882 KiB  
Article
Doxycycline Restores Gemcitabine Sensitivity in Preclinical Models of Multidrug-Resistant Intrahepatic Cholangiocarcinoma
by Annamaria Massa, Francesca Vita, Caterina Peraldo-Neia, Chiara Varamo, Marco Basiricò, Chiara Raggi, Paola Bernabei, Jessica Erriquez, Francesco Leone, Massimo Aglietta, Giuliana Cavalloni and Serena Marchiò
Cancers 2025, 17(1), 132; https://doi.org/10.3390/cancers17010132 - 3 Jan 2025
Viewed by 468
Abstract
Background/Objectives: Intrahepatic cholangiocarcinoma (iCCA) is a malignant liver tumor with a rising global incidence and poor prognosis, largely due to late-stage diagnosis and limited effective treatment options. Standard chemotherapy regimens, including cisplatin and gemcitabine, often fail because of the development of multidrug resistance [...] Read more.
Background/Objectives: Intrahepatic cholangiocarcinoma (iCCA) is a malignant liver tumor with a rising global incidence and poor prognosis, largely due to late-stage diagnosis and limited effective treatment options. Standard chemotherapy regimens, including cisplatin and gemcitabine, often fail because of the development of multidrug resistance (MDR), leaving patients with few alternative therapies. Doxycycline, a tetracycline antibiotic, has demonstrated antitumor effects across various cancers, influencing cancer cell viability, apoptosis, and stemness. Based on these properties, we investigated the potential of doxycycline to overcome gemcitabine resistance in iCCA. Methods: We evaluated the efficacy of doxycycline in two MDR iCCA cell lines, MT-CHC01R1.5 and 82.3, assessing cell cycle perturbation, apoptosis induction, and stem cell compartment impairment. We assessed the in vivo efficacy of combining doxycycline and gemcitabine in mouse xenograft models. Results: Treatment with doxycycline in both cell lines resulted in a significant reduction in cell viability (IC50 ~15 µg/mL) and induction of apoptosis. Doxycycline also diminished the cancer stem cell population, as indicated by reduced cholangiosphere formation. In vivo studies showed that while neither doxycycline nor gemcitabine alone significantly reduced tumor growth, their combination led to marked decreases in tumor volume and weight at the study endpoint. Additionally, metabolic analysis revealed that doxycycline reduced glucose uptake in tumors, both as a monotherapy and more effectively in combination with gemcitabine. Conclusions: These findings suggest that doxycycline, especially in combination with gemcitabine, can restore chemotherapy sensitivity in MDR iCCA, providing a promising new strategy for improving outcomes in this challenging disease. Full article
(This article belongs to the Collection Primary Liver Cancer)
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15 pages, 1134 KiB  
Article
Does Personality Influence the Quality of Life of Patients with Brain Tumors Treated with Radiotherapy?
by Agnieszka Pilarska, Anna Pieczyńska, Krystyna Adamska and Katarzyna Hojan
Cancers 2025, 17(1), 131; https://doi.org/10.3390/cancers17010131 - 3 Jan 2025
Viewed by 390
Abstract
Background: Understanding the role of personality traits in shaping treatment outcomes is crucial given the multifaceted challenges posed by brain tumors and the significant adverse impact of radiotherapy (RT) on patients’ well-being. Purpose: This study aimed to provide insights into how personality traits [...] Read more.
Background: Understanding the role of personality traits in shaping treatment outcomes is crucial given the multifaceted challenges posed by brain tumors and the significant adverse impact of radiotherapy (RT) on patients’ well-being. Purpose: This study aimed to provide insights into how personality traits affect psychosocial well-being and quality of life during RT in patients with high-grade malignant brain tumors. Methods: Personality traits in patients with high-grade glioma were assessed using the Eysenck Personality Questionnaire-Revised (EPQ-R). Quality of life was analyzed using EORTC questionnaires: the Questionnaire-Core 30 (QLQ-C30) and the Brain Cancer Module (QLQ-BN20). Patients were evaluated before RT, immediately after 6 weeks of RT, and 3 months post-RT. Results: Neuroticism predicted emotional function only three months post-RT. Extraversion decreased quality of life in global health status (third assessment), role function (second assessment), and emotional function (second and third assessments) but improved cognitive (first assessment) and social function (second assessment). The trait associated with lying was linked to a better quality of life in all domains except physical and cognitive function. Anxiety predicted a lower quality of life in brain tumor patients across all domains at various stages of RT treatment. Conclusions: This study advances our understanding of the psychosocial aspects of brain tumor care by highlighting the influence of personality traits on quality-of-life outcomes during RT. Identifying high-grade glioma patients at greater risk of a diminished quality of life based on personality profiles allows healthcare professionals to tailor interventions to address specific psychosocial needs, ultimately enhancing patient outcomes and holistic care during oncological treatment. Full article
(This article belongs to the Section Cancer Survivorship and Quality of Life)
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18 pages, 4377 KiB  
Article
Deep Convolutional Framelets for Dose Reconstruction in Boron Neutron Capture Therapy with Compton Camera Detector
by Angelo Didonna, Dayron Ramos Lopez, Giuseppe Iaselli, Nicola Amoroso, Nicola Ferrara and Gabriella Maria Incoronata Pugliese
Cancers 2025, 17(1), 130; https://doi.org/10.3390/cancers17010130 - 3 Jan 2025
Viewed by 398
Abstract
Background: Boron neutron capture therapy (BNCT) is an innovative binary form of radiation therapy with high selectivity towards cancer tissue based on the neutron capture reaction 10B(n,α)7Li, consisting in the exposition of patients to neutron beams after administration [...] Read more.
Background: Boron neutron capture therapy (BNCT) is an innovative binary form of radiation therapy with high selectivity towards cancer tissue based on the neutron capture reaction 10B(n,α)7Li, consisting in the exposition of patients to neutron beams after administration of a boron compound with preferential accumulation in cancer cells. The high linear energy transfer products of the ensuing reaction deposit their energy at the cell level, sparing normal tissue. Although progress in accelerator-based BNCT has led to renewed interest in this cancer treatment modality, in vivo dose monitoring during treatment still remains not feasible and several approaches are under investigation. While Compton imaging presents various advantages over other imaging methods, it typically requires long reconstruction times, comparable with BNCT treatment duration. Methods: This study aims to develop deep neural network models to estimate the dose distribution by using a simulated dataset of BNCT Compton camera images. The models pursue the avoidance of the iteration time associated with the maximum-likelihood expectation-maximization algorithm (MLEM), enabling a prompt dose reconstruction during the treatment. The U-Net architecture and two variants based on the deep convolutional framelets framework have been used for noise and artifact reduction in few-iteration reconstructed images. Results: This approach has led to promising results in terms of reconstruction accuracy and processing time, with a reduction by a factor of about 6 with respect to classical iterative algorithms. Conclusions: This can be considered a good reconstruction time performance, considering typical BNCT treatment times. Further enhancements may be achieved by optimizing the reconstruction of input images with different deep learning techniques. Full article
(This article belongs to the Section Methods and Technologies Development)
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